Baseline Serum Osteopontin Levels Predict the Clinical Effectiveness of Tocilizumab but Not Infliximab in Biologic-Naïve Patients with Rheumatoid Arthritis: A Single-Center Prospective Study at 1 Year (the Keio First-Bio Cohort Study)

Abstract

Objective: To explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naïve rheumatoid arthritis patients.

Methods: Consecutive biologic-naïve patients with rheumatoid arthritis initiating infliximab (n = 57) or tocilizumab (n = 70) treatment were included in our prospective cohort study. Our cohort started in February 2010, and the patients observed for at least 1 year as of April 2013 were analysed. We assessed baseline variables including patients' characteristics (age, sex, disease duration, prednisolone dose, methotrexate dose, other disease-modifying antirheumatic drug use, Clinical Disease Activity Index [CDAI]) and serum biomarker levels (C-reactive protein, immunoglobulin M-rheumatoid factor, anti-cyclic citrullinated protein/peptide antibodies, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-17, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, bone alkaline phosphatase, osteonectin, osteopontin) to extract factors associated with clinical remission (CDAI ≤ 2.8) at 1 year using univariate analyses, and the extracted factors were entered into a multivariate logistic regression model. Similar analyses were also performed for Simplified Disease Activity Index (SDAI) remission (≤ 3.3) and Disease Activity Score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR) remission (< 2.6).

Results: There were no significant differences in the baseline characteristics except for methotrexate use between the groups. In the multivariate analyses, the low baseline osteopontin levels (OR 0.9145, 95% CI 0.8399-0.9857) were identified as predictors of CDAI remission in the tocilizumab group, whereas no predictors of CDAI remission were found in the infliximab group. Similar results were obtained when using SDAI and DAS28-ESR remission criteria.

Conclusion: Baseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic-naïve patients with rheumatoid arthritis. Our prediction model provided insights into how to optimize the choice of biologics and warrants external validation in other cohorts.

Fig 1. Categorical changes in clinical indices.

(A) Clinical Disease Activity Index (CDAI), (B) Simplified Disease Activity Index (SDAI), and (C) disease activity score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR), over 1-year treatment of infliximab (IFX) or tocilizumab (TCZ). H, high disease activity; M, moderate disease activity; L, low disease activity; R, remission.

Fig 2. Predictive ability of osteopontin for clinical remission in patients with RA who received tocilizumab (TCZ) or infliximab (IFX).

(A) Logistic regression analysis showing significant association of increasing baseline osteopontin (OPN) levels with decreasing predicted probability of achieving Clinical Disease Activity Index (CDAI) remission at 1 year in the TCZ (tocilizumab) group. (B) ROC curve showing a cut-off baseline OPN level of 17.3 ng/mL, discriminating between CDAI remission and non-remission at 1 year in the TCZ group, with a sensitivity of 66% and a specificity of 80%. (C) Logistic regression analysis showing no significant association of baseline OPN levels with predicted probability of achieving CDAI remission at 1 year in the IFX (infliximab) group. Categorical changes in clinical indices such as (D) CDAI, (E) Simplified Disease Activity Index (SDAI), and (F) disease activity score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR) over 1-year treatment of TCZ or IFX, stratified by low or high baseline OPN levels (cut-off: 17.3 ng/mL). H, high disease activity; M, moderate disease activity; L, low disease activity; R, remission.